Administration of influenza vaccine subcutaneously to a 4 year old with hemophilia

1/22/2013
We have a 4 year old patient with a history of hemophilia and an egg allergy, no history of asthma. His hematologist wanted him to have a Influenza vaccine, but wondered if this could be done subcutaneously or if the flumist had been looked into during the studies of flu vaccine administration to egg allergic kids. We want to find out how many egg allergic people received flumist without issue in the studies. The hematologist said if we had to do the vaccine IM, he would need to get a factor infusion first which is extremely expensive. So IM administration is not a feasible option. Epipen would be the only IM exception to the rule. So has the Flumist vaccine been safely administered to egg allergic patients and if so is this now a common practice?

A:

Thank you for your inquiry.

There are three issues that are brought up by your question. The first is related to the safety of administration of influenza vaccine to a child with a history of egg allergy. We have dealt with that issue on many previous occasions on our Ask the Expert website. For your convenience, I have copied below the most recent responses to this question, and as you can see, it is considered safe for you to immunize this child with trivalent vaccine.

The second issue is related to the efficacy of subcutaneous versus intramuscular injection. Unfortunately I cannot give you a definitive answer in this regard, but there are some data, at least in the elderly, which gives you reassurance that subcutaneous administration is equally effective in inducing an antibody response (see abstract copied below). And in children, the worry about the response to immunization is less, and I would feel that subcutaneous administration would be effective. If there is any further concern in this regard, you could immunize subcutaneously on two occasions three weeks apart. So in summary subcutaneous immunization would be a viable option.

The third issue relates to the safety of Flumist in this situation. At the time of a previous response to this question there were no data available upon which to formulate a definitive answer. But I am going to ask Dr. John Kelso, who is an internationally recognized authority in this area, and who issued our last response related to the safety of the administration of FluMist to an egg-allergic patient, to respond specifically to this issue. When I receive Dr. Kelso’s response, I will forward it to you.

Thank you again for your inquiry.

Phil Lieberman, M.D.

Allergy to egg and the administration of influenza vaccine
Question posted 11/8/2012:
Do you think it is a good idea for healthcare providers who give the flu vaccine to still ask "Do you have a h/o allergy to egg?" before giving a flu vaccine? I have been staying up-to-date with reading all the articles about flu vaccine and egg allergy, most of which are being pumped out by University of Michigan allergy clinic. It does not seem like there is ANY correlation between likelihood of having a probable allergic reaction to a flu vaccine and having egg allergy. So, when is this annoyance of having to ask about egg allergy on the flu vaccine questionnaire going to stop?

Answer from Dr. Lieberman:
We received a response from Dr. Matthew Greenhawt. Thank you again for your inquiry, and we hope this response is helpful to you.

Response from Dr. Matthew Greenhawt:
"This is a great question. I think that we can confidently say that the injectable trivalent influenza vaccine (TIV) is safe for egg allergic individuals, irrespective of a past severe reaction to egg. These individuals can receive the vaccine without vaccine skin testing, and as a single dose. Several recent studies have demonstrated these concepts. Neither the JTFPP nor the ACIP guidelines recommend that TIV be withheld in egg allergic individuals. These guidelines do differ slightly in the recommendations of what setting is best for certain egg allergic individuals to receive the vaccine (e.g., at the primary care provider office or at the allergist office).

Answering your question requires us to consider that various types of health care providers offer TIV vaccination. The questionnaire item was designed to screen-out egg allergic individuals when TIV was contraindicated in this population. Though this recommendation has changed, the questionnaire item still has some application. In the JTFPP guidelines, it advised that egg allergic individuals not receive TIV at walk-in pharmacy based clinic, employee-health or other type of clinic where there was not direct office-based physician supervision (e.g. mass walk-in flu shot clinics not held at a physician's office where there is full access to one's medical record, such as may be offered by a large employer or a hospital occupational health service). Therefore, the questionnaire item serves a purpose to identify egg allergic individuals and prevent them from receiving TIV outside of either their primary care provider's or allergist's office. Keep in mind that the ACIP still recommends that only patients with a history of just hives with egg consumption receive TIV in the primary care office setting, and that more severe egg allergic individuals be vaccinated at the allergist.

In the primary care physician office setting, there is very little need to ask this item on a questionnaire. The egg allergy history should be in the medical record and the provider ordering the vaccine should have reviewed that and determined if TIV was OK to administer in his/her office. However, there is a chance that the allergy history may be overlooked, especially if that provider is not the primary party managing the allergy, so the questionnaire item may then serve some purpose as a double-check mechanism to make sure that the individual's allergy history is reviewed and that TIV can be administered in that particular setting.

In an allergy clinic, obviously, such a questionnaire would clearly not be necessary. However, it should be recognized that this questionnaire may required by the provider's health care system, irrespective of the overwhelming evidence that it is unnecessary to ask. Over time, I do expect that this specific item will not be included on future versions of this questionnaire, but this may require further evidence demonstrating that it is safe to provide TIV to egg allergic individuals in a non-physician office setting."

New guidelines regarding the administration of influenza vaccine to a patient with a history of egg allergy

Question posted 7/22/2012:
I was reading a response regarding administration of the flu vaccine to an egg allergic patient. Would your recommendations change after AAAAI news feed published the following articles? Has the CDC OR AAAAI published a statement protecting allergists medico-legally if we were to give the flu vaccine to all patients even those with history of anaphylaxis to egg in 1 dose in our allergy offices? Have you advised PCPs to give the flu vaccine to egg allergic patients with history of hives in their offices?

eNews
Egg Allergy and Influenza Vaccine

Answer from Dr. Lieberman:
For the sake of our readers, I have copied the summary of the reference to which you referred. It is an update to the Immunization (vaccination) Practice Parameters that is concerned specifically with immunization to influenza vaccine in patients who give a history of an allergic reaction to eggs.

Summary
"The risk of an allergic reaction to influenza vaccine in patients with egg allergy is very low, likely due to the very low amount of ovalbumin in the vaccines. Any such theoretical risk is far outweighed by the very real risk of such patients remaining unvaccinated. Thus all patients with egg allergy of any severity, including anaphylaxis, should receive influenza vaccine. Skin testing with the vaccine and dividing the dose are not necessary. The injectable vaccine should be administered in a medical setting where anaphylaxis can be recognized and treated should it occur. For those with a history of hives only after egg ingestion, the vaccine can be administered in the primary care provider's office. For those with more serious reactions to egg ingestion, the vaccine should be administered in an allergist's office."

The summary is self-explanatory and is a reiteration of the essence of this document. I personally think it is important to read the document in its entirety in order to be able to understand the evidence upon which this summary is based.

Having said that, I will try and answer your specific questions:

My recommendations would now be consistent with this document which was published in July of 2012.

My personal interpretation of this document is that it is not intended to be a "medical/legal" text, but rather a summary of the best data we have to guide us in the administration of influenza vaccine with a history of egg allergy. The medical/legal implications of this document would require an attorney, and I think each individual implementing the guidelines will have to make their own judgment as to medical risks in this regard.

Since this document came out in July, and we have not reached the influenza vaccination season, I have not acted upon the recommendations in this document. My sense is that I will take into consideration each patient separately and make judgments accordingly as to which patients I should personally evaluate, using these guidelines for the basis of my judgment.”

Influenza Vaccination and Warfarin Anticoagulation: A Comparison of Subcutaneous and Intramuscular Routes of Administration in Elderly Men

Jeffrey C. Delafuente M.SPharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume 18, Issue 3, pages 631–636, May-June 199
Study Objectives
To determine if subcutaneous administration of influenza vaccine is as immunogenic as the intramuscular route, and to evaluate the frequency of local adverse events associated with both routes in elderly anticoagulated men.Design. Single-blind, prospective study of consecutively enrolled subjects.Setting. Ambulatory clinic at a university-affiliated Veterans Affairs medical center.Patients. Twenty-six men age 60 years or older, receiving therapeutic dosages of warfarin.
Interventions. Subjects were randomized to receive either intramuscular or subcutaneous injection of a standard trivalent influenza vaccine.Measurements and Main Results. Serum antibody titers to the vaccine's components were measured at baseline, and 6 weeks and 4 months after vaccination. Both routes of administration induced comparable serum antibody titers. There were no differences in adverse events at administration sites between routes of administration.Conclusions. Elderly individuals are able to mount an immune response to influenza vaccine and produce antibody concentrations deemed protective. The routes of administration are similarly effective at inducing an immune response. The intramuscular route in anticoagulated elderly men does not commonly result in local bleeding complications.

Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

We have received a response from Dr. John Kelso regarding your Ask the Expert inquiry. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. John Kelso:
There have been now 28 published studies involving >4300 egg-allergic subjects (including 656 with anaphylaxis after egg ingestion) getting influenza vaccine without any serious reactions (no respiratory distress or hypotension), and with only a low rate of minor reactions (hives, mild wheezing). The rate of reactions may not be any different than in non-egg allergic recipients. Thus it appears that the amount of ovalbumin in the vaccine is too low to cause a reaction. This has led to the current recommendations from the CDC's Advisory Committee on Immunization Practices and the AAP that egg allergic patients should receive annual influenza vaccines, but be observed for 30 minutes afterwards. If ingestion of egg has caused only hives, the vaccine can be administered in a primary care setting. If ingestion of egg has caused more serious reactions, the vaccine should be given in an allergist's office. The recommendation is that injectable influenza vaccine be used only because all of these studies have involved the injectable vaccine. The package insert for the live attenuated intranasal influenza vaccine, FluMist, indicates that it also contains a very small amount of egg protein in the form of ovalbumin (<0.24 mcg/dose). This is about the same amount of ovalbumin per dose as the injectable vaccines. There are no published studies of giving the intranasal vaccine to egg allergic patients. Just as with the injectable vaccine, there have been a few reports of anaphylaxis to the intranasal vaccine, although none of these occurred in patients reported to be egg allergic. There are anecdotal reports of egg allergic children receiving the FluMist without reaction. In this particular patient, where the injection could cause bleeding and would require a factor infusion ahead of time, I would certainly think that the risk, if any, of receiving the intranasal influenza vaccine would be less than the risk associated with the injection. Thus I would recommend that the child received FluMist and be observed for 30 minutes afterwards in a setting where an allergic reaction can be recognized and treated if it occurred.